NM_001009944.3:c.10768C>T

Variant names:

• chr16-2093864-G-A
• rs116114803
• NM_001009944.3:c.10768C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001009944.3(PKD1):​c.10768C>T​(p.Leu3590Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0315 in 1,569,998 control chromosomes in the GnomAD database, including 941 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (63 hom., cov: 33)
  • Exomes 𝑓: 0.032 (878 hom.)
• Consequence: PKD1 NM_001009944.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.335
• Publications: 11 publications found

Genes affected

PKD1 (HGNC:9008): (polycystin 1, transient receptor potential channel interacting) This gene encodes a member of the polycystin protein family. The encoded glycoprotein contains a large N-terminal extracellular region, multiple transmembrane domains and a cytoplasmic C-tail. It is an integral membrane protein that functions as a regulator of calcium permeable cation channels and intracellular calcium homoeostasis. It is also involved in cell-cell/matrix interactions and may modulate G-protein-coupled signal-transduction pathways. It plays a role in renal tubular development, and mutations in this gene cause autosomal dominant polycystic kidney disease type 1 (ADPKD1). ADPKD1 is characterized by the growth of fluid-filled cysts that replace normal renal tissue and result in end-stage renal failure. Splice variants encoding different isoforms have been noted for this gene. Also, six pseudogenes, closely linked in a known duplicated region on chromosome 16p, have been described. [provided by RefSeq, Oct 2008]

PKD1-AS1 (HGNC:56035): (PKD1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 16-2093864-G-A is Benign according to our data. Variant chr16-2093864-G-A is described in ClinVar as Benign. ClinVar VariationId is 256894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.335 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0231 (3514/152294) while in subpopulation NFE AF = 0.0379 (2577/68000). AF 95% confidence interval is 0.0367. There are 63 homozygotes in GnomAd4. There are 1656 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 63 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009944.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1	NM_001009944.3	MANE Select	c.10768C>T	p.Leu3590Leu	synonymous	Exon 36 of 46	NP_001009944.3
	PKD1	NM_000296.4		c.10765C>T	p.Leu3589Leu	synonymous	Exon 36 of 46	NP_000287.4
	PKD1-AS1	NR_135175.1		n.303+852G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1	ENST00000262304.9	TSL:1 MANE Select	c.10768C>T	p.Leu3590Leu	synonymous	Exon 36 of 46	ENSP00000262304.4
	PKD1	ENST00000423118.5	TSL:1	c.10765C>T	p.Leu3589Leu	synonymous	Exon 36 of 46	ENSP00000399501.1
	PKD1	ENST00000472659.1	TSL:3	n.205C>T		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes AF: 0.0231 AC: 3512 AN: 152176 Hom.: 63 Cov.: 33

Gnomad AFR AF: 0.00632

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0114

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00786

Gnomad FIN AF: 0.0296

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0379

Gnomad OTH AF: 0.0196

GnomAD2 exomes AF: 0.0220 AC: 4115 AN: 187406 AF XY: 0.0223

Gnomad AFR exome AF: 0.00659

Gnomad AMR exome AF: 0.00782

Gnomad ASJ exome AF: 0.0173

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0371

Gnomad NFE exome AF: 0.0350

Gnomad OTH exome AF: 0.0233

GnomAD4 exome AF: 0.0324 AC: 45921 AN: 1417704 Hom.: 878 Cov.: 33 AF XY: 0.0319 AC XY: 22428 AN XY: 703030

African (AFR) AF: 0.00498 AC: 162 AN: 32534

American (AMR) AF: 0.00834 AC: 338 AN: 40534

Ashkenazi Jewish (ASJ) AF: 0.0166 AC: 424 AN: 25558

East Asian (EAS) AF: 0.0000532 AC: 2 AN: 37580

South Asian (SAS) AF: 0.0114 AC: 937 AN: 82214

European-Finnish (FIN) AF: 0.0348 AC: 1355 AN: 38882

Middle Eastern (MID) AF: 0.00332 AC: 19 AN: 5726

European-Non Finnish (NFE) AF: 0.0376 AC: 41165 AN: 1095710

Other (OTH) AF: 0.0258 AC: 1519 AN: 58966

GnomAD4 genome AF: 0.0231 AC: 3514 AN: 152294 Hom.: 63 Cov.: 33 AF XY: 0.0222 AC XY: 1656 AN XY: 74462

African (AFR) AF: 0.00630 AC: 262 AN: 41570

American (AMR) AF: 0.0114 AC: 175 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0167 AC: 58 AN: 3468

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5176

South Asian (SAS) AF: 0.00849 AC: 41 AN: 4830

European-Finnish (FIN) AF: 0.0296 AC: 314 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0379 AC: 2577 AN: 68000

Other (OTH) AF: 0.0194 AC: 41 AN: 2114

Alfa AF: 0.0241 Hom.: 24

Bravo AF: 0.0210

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Apr 25, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Polycystic kidney disease, adult type Benign:2

May 08, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

May 15, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Oct 27, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 19686598, 11058904, 15772804)

Autosomal dominant polycystic kidney disease Benign:1

Jan 01, 2019

Molecular Genetics of Inherited Kidney Disorders Laboratory, Garvan Institute of Medical Research

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.8
DANN	Benign	0.72
PhyloP100		0.34
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs116114803; hg19: chr16-2143865;